4:41 PM
Feb 08, 2018
 |  BC Innovations  |  Product R&D

R is for readout

AZ turns in a report card for its 5R framework

Editor's Note: This article was updated on Feb 15, 2018 at 10:04 AM PST

While AstraZeneca plc gets credit for transparency in publishing its metrics on R&D productivity, the data cover well-established targets addressed by conventional modalities. The more telling test for its “5R framework” will be whether it can accelerate development in white space areas with novel biology.

AstraZeneca’s analysis, published last month in Nature Reviews Drug Discovery, follows up on a 2014 analysis in the same journal in which the company took stock of pipeline failures from 2005-2010. Compared with industry averages, AstraZeneca was bringing more compounds into late stage development, but they were failing at a higher rate due primarily to insufficient safety, target validation, proof of target engagement or patient stratification.

AstraZeneca designed a framework to identify and advance programs designed to get five factors “right:” the target, the tissue where the target is engaged, safety, the patient population and the commercial potential. It began implementing the framework throughout its R&D in 2012.

Now the company has reported readouts for the framework, showing it boosted the rate of projects progressing from candidate nomination to Phase III completion to 19% between 2012-2016, up from 4% between 2005-2010. Since implementing the framework, AstraZeneca also shrunk program costs and cycle times, expanded its work on patient stratification and companion diagnostics, and shifted compound attrition further upstream in the R&D process.

The authors highlighted specific methods for target discovery, compound screening, in vivo assessment, toxicity testing and patient selection that they believe drove the productivity jump.

Mene Pangalos, lead author and EVP of AstraZeneca’s Innovative Medicines and Early Development (IMED) Biotech Unit, told BioCentury the company didn’t move programs forward unless they met the framework’s standards, such as having an explicit patient stratification strategy. “There were some teeth to this,” he said.

“I clearly think pharmas are doing collectively a better job. A framework like the 5Rs is happening everywhere, and that’s right.”

David Grainger, Medicxi

Few companies have disclosed R&D data with such granularity.

However, three KOLs who spoke with BioCentury said there is little evidence AstraZeneca has broken a mold in drug development rather than followed industry norms.

Medicinal chemist and industry commentator Derek Lowe told BioCentury: “I think it’s good to look at these things, but on the other hand, I don’t think that any of the “5R” criteria are the least bit controversial in the industry. Every drug company could put that slide up and no one would complain, is my guess.”

Medicxi’s David Grainger, who is also a co-founder of Methuselah Health Inc. and Epsilon-3 Bio Ltd., thinks the improvements reflect better practices across the industry.

“I clearly think pharmas are doing collectively a better job. A framework like the 5Rs is happening everywhere, and that’s right. One would hope that it would significantly increase productivity of early stage R&D,” said Grainger.

Industry consultant Steve Schow noted the portfolio was mostly centered on me-too targets and medical indications that are already well treated, which indicated an approach of managed risk rather than innovation and risk-taking. “They appear to...

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